Fig. 1

Study overview. The figure shows the highlights of our study. First, we performed a microbiome genome-wide association study in a Chinese population (step A). We validated significant genetic variants reported in previous studies and replicated our results in an independent cohort. Second, we investigated the causal relationship between the gut microbiome and complex human diseases using host genetics as instrumental variables for bidirectional Mendelian randomization (MR) analysis (step B). For the analysis of the effects of the gut microbiome on complex traits, we used publicly available GWAS summary statistics of complex traits (n = 58) and diseases (type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), colorectal cancer (CRC) and rheumatoid arthritis) reported by BioBank Japan [19,20,21,22,23,24]. For the reverse MR analyses, the diseases of interest included T2DM (cases: 7,109; non-cases: 86,022), AF (cases: 8,180; non-cases: 28,612), coronary artery disease (cases: 1,515; non-cases: 5019), chronic kidney disease (n = 71,149), Alzheimer’s disease (cases: 477; non-cases: 442), CRC (cases: 8027; non-cases: 22,577) and prostatic cancer (cases: 495; non-cases: 640) reported in the previous large-scale GWASs in East Asians [19, 25,26,27,28,29,30]. Finally, we identified common and distinct gut microbiome features across different diseases (step C)